The overall goal of the Dartmouth SBRP Program Project, Toxic Metals in the Northeast: From Biological to Environmental Implications, is to determine the impact of toxic metals found at Superfund sites, at other waste sites, and in the environment on adverse effects on human health and the environment. Eight of the twenty-two agents on the ATSDR priority list. Over 60% of all Superfund sites contain significant toxic metal contamination, and more than 70% of these contain arsenic, which is the top ATSDR agent of concern. The distinct and program-wide focus of this research program is on toxic metals, and particularly on arsenic, which is being examined in all their goals and scientific focus, including chromium, nickel, cadmium, mercury, cobalt and lead. This program consists of five biomedical projects (Projects 1-5), two non-biomedical projects (Projects 6, 7), and three program support cores (Molecular Biology, Trace Metals Analysis and Biostatistics), plus an Administrative core, Training laboratory investigations on the cellular and molecular mechanisms of toxic metal actions in humans and include Project 1 (arsenic-induced vascular disease), Project 2 (arsenic- and chromium- induced cancer), Project 3 (arsenic effects on xenobiotic metabolism) and Project 5 (interactions of toxic metals with cellular proteins). The second includes Project 4 (human epidemiology of arsenic and skin and bladder cancer), Project 6 (sources, fate and third area involves development and implementation of molecular biomarkers of toxic metal exposure and health elucidate the sub-set of genes, mRNAs and proteins whose expression is specifically modified by toxic metal mechanistic laboratory studies and in the ecology and epidemiology projects. The multi- disciplinary nature of this program, combined with its unique program- wide focus on arsenic and other toxic metals, is designed to create and foster an environment for truly inter-disciplinary yet focused research, training and outreach.